Evaluation of Long-Term Safety and Tolerability of ETC-1002 in High-Risk Patients With Hyperlipidemia and High CV Risk (CLEAR Harmony)
Sponsor
Esperion Therapeutics, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02666664
Collaborator
(none)
2,230
104
2
26.2
21.4
0.8
Study Details
Study Description
Brief Summary
The purpose of this study is to see if ETC-1002 (bempedoic acid) is safe and well-tolerated versus placebo in patients with high cardiovascular risk and elevated LDL cholesterol that is not adequately controlled by their current therapy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
2230 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-blind, Placebo-controlled, Multicenter Long-term Safety and Tolerability Study of ETC-1002 in Patients With Hyperlipidemia at High Cardiovascular Risk Who Are Not Adequately Controlled by Their Lipid-Modifying Therapy
Actual Study Start Date
:
Jan 21, 2016
Actual Primary Completion Date
:
Feb 21, 2018
Actual Study Completion Date
:
Mar 28, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ETC-1002 ETC-1002 180 mg/day |
Drug: ETC-1002
ETC-1002 180 mg tablets taken orally, once per day. Patients remain on ongoing statin therapy (not study provided)
Other Names:
|
| Placebo Comparator: Placebo Placebo control |
Drug: Placebo
Matching placebo tablets taken orally, once per day. Patients remain on ongoing statin therapy (not study provided)
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) [Up to approximately 52 weeks]
TEAEs, defined as adverse events (AEs) that began or worsened in severity after the first dose of double-blind study drug and up to 30 days after receiving the last dose of double-blind study drug, were collected and reported.
- Percentage of Participants With Adjudicated Major Adverse Cardiovascular Event [Up to approximately 52 weeks]
TEAEs, defined as AEs that began or worsened in severity after the first dose of double-blind study drug and up to 30 days after receiving the last dose of double-blind study drug, were collected and reported. Cardiovascular events were considered as adverse events of special interest. Treatment-emergent = TE.
- Percentage of Participants With the Indicated Event of Special Interest: Creatine Kinase Elevations [Up to approximately 52 weeks]
TEAEs of special interest (AESIs) were predefined and monitored throughout the study. Creatine kinase elevations were assessed using the following preferred term: Blood creatine phosphokinase increased (system organ class: investigations).
- Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders [Up to approximately 52 weeks]
Treatment-emergent AESIs were predefined and monitored throughout the study. TEAEs potentially related to hepatic events were assessed using the following preferred terms and laboratory abnormalities: aspartate aminotransferase (AST) increased, Alanine aminotransferase (ALT) increased, Hepatic enzyme increased, Blood bilirubin increased, liver function test (LFT) abnormal, LFT increased, hepatic enzyme abnormal, transaminases increased, potential Hy's Law cases (PHLC) [AST and (&)/or ALT >3 x upper limit of normal (ULN) with concurrent total bilirubin >2 x ULN], AST and/or ALT >3 x ULN, and total bilirubin >2 x ULN (system organ class: investigations). AST and ALT values were repeated and confirmed. "Repeated and confirmed" was defined as a participant having the last on-study LFT > x ULN, the last on-treatment LFT > x ULN, or LFT > x ULN followed by another LFT > x ULN.
- Percentage of Participants With the Indicated Event of Special Interest: Hypoglycemia [Up to approximately 52 weeks]
Treatment-emergent AESIs were predefined and monitored throughout the study. Hypoglycemia was assessed using the following preferred terms: hypoglycaemia (system organ class: metabolism and nutrition disorders); blood glucose abnormal and blood glucose decreased (system organ class: investigations). The percentage of unique participants is reported in the "Overall hypoglycemia AESIs" category; a participant could have been represented in more than one of the individual hypoglycemia AESIs.
- Percentage of Participants With the Indicated Event of Special Interest: Metabolic Acidosis [Up to approximately 52 weeks]
Treatment-emergent AESIs were predefined and monitored throughout the study. Metabolic acidosis was assessed using the preferred term metabolic acidosis (system organ class: metabolism and nutrition disorders).
- Percentage of Participants With the Indicated Event of Special Interest: Muscular Disorder [Up to approximately 52 weeks]
Treatment-emergent AESIs were predefined and monitored throughout the study. Muscular safety was assessed using the following preferred terms and laboratory abnormalities: myalgia, muscle spasms, pain in extremity, muscular weakness (system organ class: musculoskeletal and connective tissue disorders), and creatine kinase >5 ULN (repeated and confirmed). The percentage of unique participants is reported in the "Overall muscular disorder AESIs" category; a participant could have been represented in more than one of the individual muscular disorder AESIs.
- Percentage of Participants With the Indicated Event of Special Interest: Neurocognitive Disorder [Up to approximately 52 weeks]
Treatment-emergent AESIs were predefined and monitored throughout the study. Neurocognitive disorder was assessed using the following preferred terms: memory impairment, amnesia, and cognitive disorder (system organ class: nervous system disorders); confusional state and disorientation (system organ class: psychiatric disorders). The percentage of unique participants is reported in the "Overall neurocognitive disorder AESIs" category; a participant could have been represented in more than one of the individual neurocognitive disorder AESIs.
- Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus [Up to approximately 52 weeks]
Treatment-emergent AESIs were predefined and monitored throughout the study. New onset or worsening diabetes was assessed using the following preferred terms: type 2 diabetes mellitus, diabetes mellitus, hyperglycaemia, glucose tolerance impaired, diabetes mellitus inadequate control, and impaired fasting glucose (system organ class: metabolism and nutrition disorders); blood glucose increased, glycosylated haemoglobin increased, blood glucose abnormal, and glucose urine present (system organ class: investigations); and glycosuria (system organ class: renal and urinary disorders). The percentage of unique participants is reported in the "Overall new onset/worsening diabetes mellitus AESIs" category; a participant could have been represented in more than one of the individual new onset/worsening diabetes mellitus AESIs.
- Percentage of Participants With the Indicated Event of Special Interest: Renal Disorder [Up to approximately 52 weeks]
Treatment-emergent AESIs were predefined and monitored throughout the study. TEAEs potentially related to renal events were assessed using the following preferred terms: renal failure, renal impairment, acute kidney injury (system organ class: renal and urinary disorders); blood creatinine increased, glomerular filtration rate decreased, blood urea increased, estimated glomerular filtration rate (eGFR) <30 milliliter per minute per 1.73 square meter (ml/min/1.73m^2), and change from baseline in creatinine >1 mg/dL (system organ class: investigations); and gout (system organ class: metabolism and nutrition disorders). The percentage of unique participants is reported in the "Overall renal disorder AESIs" category; a participant could have been represented in more than one of the individual renal disorder AESIs.
- Change From Baseline to Week 52 in Uric Acid (Urate) Level [Baseline and Week 52]
Blood samples were drawn at defined time points during the course of the study to monitor uric acid (urate) levels.
- Change From Baseline to Week 52 in Creatinine Level [Baseline and Week 52]
Blood samples were drawn at defined time points during the course of the study to monitor creatinine levels.
- Change From Baseline to Week 52 in Hemoglobin Level [Baseline and Week 52]
Blood samples were drawn at defined time points during the course of the study to monitor hemoglobin levels.
Secondary Outcome Measures
- Percent Change From Baseline to Week 12 in Low-density Lipoprotein Cholesterol (LDL-C) [Baseline; Week 12]
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: [(LDL-C value at Week 12 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen. Least Square mean= LS mean. Percent change was analyzed using the analysis of covariance (ANCOVA) method, which included treatment, randomization stratum as factors, and baseline value as covariate.
- Absolute Change From Baseline to Week 12 in LDL-C [Baseline; Week 12]
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Absolute change from baseline was calculated as: LDL-C value at Week 12 minus Baseline value. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen.
Other Outcome Measures
- Percent Change From Baseline to Week 24 in LDL-C [Baseline; Week 24]
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: [(LDL-C value at Week 24 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate.
- Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) [Baseline; Week 12]
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for non-HDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: [(non-HDL-C value at Week 12 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate.
- Percent Change From Baseline to Week 12 in Total Cholesterol (TC) [Baseline; Week 12]
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for TC. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: [(TC value at Week 12 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate.
- Percent Change From Baseline to Week 12 in Apolipoprotein B (apoB) [Baseline; Week 12]
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for apoB. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: [(apoB value at Week 12 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate.
- Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP) [Baseline; Week 12]
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for hsCRP. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: [(hsCRP value at Week 12 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate.
- Percent Change From Baseline to Week 52 in LDL-C [Baseline; Week 52]
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: [(LDL-C value at Week 52 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate.
- Percent Change From Baseline to Week 24 in Non-HDL-C [Baseline; Week 24]
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for non-HDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: [(non-HDL-C value at Week 24 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed.
- Percent Change From Baseline to Week 52 in Non-HDL-C [Baseline; Week 52]
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for non-HDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: [(non-HDL-C value at Week 52 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed.
- Percent Change From Baseline to Week 24 in TC [Baseline; Week 24]
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for TC. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: [(TC value at Week 24 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed.
- Percent Change From Baseline to Week 52 in TC [Baseline; Week 52]
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for TC. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: [(TC value at Week 52 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed.
- Percent Change From Baseline to Week 24 in apoB [Baseline; Week 24]
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for apoB. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: [(apoB value at Week 24 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed
- Percent Change From Baseline to Week 52 in apoB [Baseline; Week 52]
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for apoB. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: [(apoB value at Week 52 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed.
- Percent Change From Baseline to Week 24 in hsCRP [Baseline; Week 24]
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for hsCRP. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: [(hsCRP value at Week 24 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed.
- Percent Change From Baseline to Week 52 in hsCRP [Baseline; Week 52]
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for hsCRP. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: [(hsCRP value at Week 52 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed.
- Percentage of Participants Achieving LDL-C <70 mg/dL at Week 12, 24, and 52 [Week 12, Week 24, and Week 52]
The percentage of participants who achieved lowering in lipid values of LDL-C below 70 mg/dL have been reported. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Observed data was used for the analysis, no imputation for the missing data was performed.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Fasting LDL-C ≥ 70 mg/dL
-
High cardiovascular risk (diagnosis of HeFH or ASCVD)
-
Be on maximally tolerated lipid-modifying therapy
Exclusion Criteria:
-
Total fasting triglyceride ≥500 mg/dL
-
Renal dysfunction or nephrotic syndrome or history of nephritis
-
Body Mass Index (BMI) ≥50kg/m2
-
Significant cardiovascular disease or cardiovascular event in the past 3 months
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Huntsville | Alabama | United States | ||
| 2 | Cottonwood | Arizona | United States | ||
| 3 | Phoenix | Arizona | United States | ||
| 4 | Canoga Park | California | United States | ||
| 5 | Santa Rosa | California | United States | ||
| 6 | Bridgeport | Connecticut | United States | ||
| 7 | Hartford | Connecticut | United States | ||
| 8 | Atlantis | Florida | United States | ||
| 9 | Boca Raton | Florida | United States | ||
| 10 | Crestview | Florida | United States | ||
| 11 | Crystal River | Florida | United States | ||
| 12 | Daytona Beach | Florida | United States | ||
| 13 | Lake Worth | Florida | United States | ||
| 14 | Miami Lakes | Florida | United States | ||
| 15 | Tampa | Florida | United States | ||
| 16 | Park Ridge | Illinois | United States | ||
| 17 | Iowa City | Iowa | United States | ||
| 18 | Overland Park | Kansas | United States | ||
| 19 | Covington | Kentucky | United States | ||
| 20 | Louisville | Kentucky | United States | ||
| 21 | Minden | Louisiana | United States | ||
| 22 | Monroe | Louisiana | United States | ||
| 23 | Shreveport | Louisiana | United States | ||
| 24 | Auburn | Maine | United States | ||
| 25 | Midland | Michigan | United States | ||
| 26 | Saginaw | Michigan | United States | ||
| 27 | Saint Cloud | Minnesota | United States | ||
| 28 | Tupelo | Mississippi | United States | ||
| 29 | Jefferson City | Missouri | United States | ||
| 30 | Nashua | New Hampshire | United States | ||
| 31 | Bridgewater | New Jersey | United States | ||
| 32 | Cary | North Carolina | United States | ||
| 33 | Mount Airy | North Carolina | United States | ||
| 34 | Raleigh | North Carolina | United States | ||
| 35 | Rocky Mount | North Carolina | United States | ||
| 36 | Wilmington | North Carolina | United States | ||
| 37 | Cincinnati | Ohio | United States | ||
| 38 | Sandusky | Ohio | United States | ||
| 39 | Willoughby | Ohio | United States | ||
| 40 | Hillsboro | Oregon | United States | ||
| 41 | Fort Worth | Texas | United States | ||
| 42 | Houston | Texas | United States | ||
| 43 | Katy | Texas | United States | ||
| 44 | Kingwood | Texas | United States | ||
| 45 | Orem | Utah | United States | ||
| 46 | Richmond | Virginia | United States | ||
| 47 | Puyallup | Washington | United States | ||
| 48 | Tacoma | Washington | United States | ||
| 49 | Vancouver | British Columbia | Canada | ||
| 50 | Victoria | British Columbia | Canada | ||
| 51 | Gatineau | Ontario | Canada | ||
| 52 | Mississauga | Ontario | Canada | ||
| 53 | Oshawa | Ontario | Canada | ||
| 54 | Peterborough | Ontario | Canada | ||
| 55 | Scarborough | Ontario | Canada | ||
| 56 | Chicoutimi | Quebec | Canada | ||
| 57 | Gatineau | Quebec | Canada | ||
| 58 | Longueuil | Quebec | Canada | ||
| 59 | Montréal | Quebec | Canada | ||
| 60 | Québec | Quebec | Canada | ||
| 61 | Saint-Jean-Sur-Richelieu | Quebec | Canada | ||
| 62 | St-Charles-Borromee | Quebec | Canada | ||
| 63 | Berlin | Germany | |||
| 64 | Bochum | Germany | |||
| 65 | Dresden | Germany | |||
| 66 | Essen | Germany | |||
| 67 | Frankfurt | Germany | |||
| 68 | Leipzig | Germany | |||
| 69 | Muenchen | Germany | |||
| 70 | Amsterdam | Netherlands | |||
| 71 | Arnhem | Netherlands | |||
| 72 | Eindhoven | Netherlands | |||
| 73 | Goes | Netherlands | |||
| 74 | Groningen | Netherlands | |||
| 75 | Hardenberg | Netherlands | |||
| 76 | Leiden | Netherlands | |||
| 77 | Rotterdam | Netherlands | |||
| 78 | Tilburg | Netherlands | |||
| 79 | Venlo | Netherlands | |||
| 80 | Zutphen | Netherlands | |||
| 81 | Gdansk | Poland | |||
| 82 | Gdynia | Poland | |||
| 83 | Katowice | Poland | |||
| 84 | Kraków | Poland | |||
| 85 | Poznań | Poland | |||
| 86 | Puławy | Poland | |||
| 87 | Toruń | Poland | |||
| 88 | Wroclaw | Poland | |||
| 89 | Łowicz | Poland | |||
| 90 | Łódź | Poland | |||
| 91 | Bexhill-on-Sea | United Kingdom | |||
| 92 | Birmingham | United Kingdom | |||
| 93 | Cardiff | United Kingdom | |||
| 94 | Chesterfield | United Kingdom | |||
| 95 | Chichester | United Kingdom | |||
| 96 | Chippenham | United Kingdom | |||
| 97 | Chorley | United Kingdom | |||
| 98 | Glasgow | United Kingdom | |||
| 99 | Hexham | United Kingdom | |||
| 100 | Hull | United Kingdom | |||
| 101 | Ipswich | United Kingdom | |||
| 102 | Liverpool | United Kingdom | |||
| 103 | Manchester | United Kingdom | |||
| 104 | Reading | United Kingdom |
Sponsors and Collaborators
- Esperion Therapeutics, Inc.
Investigators
- Study Director: Ron Haberman, MD, Esperion Therapeutics, Inc.
Study Documents (Full-Text)
More Information
Additional Information:
- World Health Organization Fact Sheet No. 317
- Familial Hypercholesterolemia Foundation
- National Organization for Rare Disorders - Familial Hypercholesterolemia
Publications
- Goldberg AC, Hopkins PN, Toth PP, Ballantyne CM, Rader DJ, Robinson JG, Daniels SR, Gidding SS, de Ferranti SD, Ito MK, McGowan MP, Moriarty PM, Cromwell WC, Ross JL, Ziajka PE; National Lipid Association Expert Panel on Familial Hypercholesterolemia. Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol. 2011 Jun;5(3 Suppl):S1-8. doi: 10.1016/j.jacl.2011.04.003. Epub 2011 Apr 12.
- Pinkosky SL, Newton RS, Day EA, Ford RJ, Lhotak S, Austin RC, Birch CM, Smith BK, Filippov S, Groot PHE, Steinberg GR, Lalwani ND. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nat Commun. 2016 Nov 28;7:13457. doi: 10.1038/ncomms13457.
- Pollex RL, Joy TR, Hegele RA. Emerging antidyslipidemic drugs. Expert Opin Emerg Drugs. 2008 Jun;13(2):363-81. doi: 10.1517/14728214.13.2.363 . Review.
- Sharrett AR, Ballantyne CM, Coady SA, Heiss G, Sorlie PD, Catellier D, Patsch W; Atherosclerosis Risk in Communities Study Group. Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions: The Atherosclerosis Risk in Communities (ARIC) Study. Circulation. 2001 Sep 4;104(10):1108-13.
- Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PW, Eddleman KM, Jarrett NM, LaBresh K, Nevo L, Wnek J, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK, Smith SC Jr, Tomaselli GF; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Jun 24;129(25 Suppl 2):S1-45. doi: 10.1161/01.cir.0000437738.63853.7a. Epub 2013 Nov 12. Erratum in: Circulation. 2014 Jun 24;129(25 Suppl 2):S46-8. Erratum in: Circulation. 2015 Dec 22;132(25):e396.
Responsible Party:
Esperion Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT02666664
Other Study ID Numbers:
- 1002-040
- 2015-004136-36
First Posted:
Jan 28, 2016
Last Update Posted:
May 11, 2020
Last Verified:
Apr 1, 2020
Keywords provided by Esperion Therapeutics, Inc.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | A total of 2230 participants were randomized 2:1 to either bempedoic acid or placebo. One participant was randomized to bempedoic acid treatment, but never received any dose of investigational medicinal product (IMP) i.e. study drug. |
|---|---|
| Pre-assignment Detail | The study consisted of 2 periods: a 2-week screening period and a 52-week double-blind, randomized treatment period. |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Period Title: Overall Study | ||
| STARTED | 742 | 1488 |
| COMPLETED | 706 | 1404 |
| NOT COMPLETED | 36 | 84 |
Baseline Characteristics
| Arm/Group Title | Placebo | Bempedoic Acid | Total |
|---|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | Total of all reporting groups |
| Overall Participants | 742 | 1488 | 2230 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
66.8
(8.64)
|
65.8
(9.11)
|
66.1
(8.96)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
213
28.7%
|
389
26.1%
|
602
27%
|
| Male |
529
71.3%
|
1099
73.9%
|
1628
73%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
11
1.5%
|
24
1.6%
|
35
1.6%
|
| Not Hispanic or Latino |
731
98.5%
|
1464
98.4%
|
2195
98.4%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
1
0.1%
|
2
0.1%
|
3
0.1%
|
| Asian |
8
1.1%
|
14
0.9%
|
22
1%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
2
0.1%
|
2
0.1%
|
| Black or African American |
15
2%
|
42
2.8%
|
57
2.6%
|
| White |
716
96.5%
|
1423
95.6%
|
2139
95.9%
|
| More than one race |
0
0%
|
1
0.1%
|
1
0%
|
| Unknown or Not Reported |
2
0.3%
|
4
0.3%
|
6
0.3%
|
| Cardiovascular history: atherosclerotic cardiovascular disease (ASCVD) (Count of Participants) | |||
| Yes |
727
98%
|
1449
97.4%
|
2176
97.6%
|
| No |
15
2%
|
39
2.6%
|
54
2.4%
|
| Cardiovascular history: heterozygous familial hypercholesterolemia (HeFH) (Count of Participants) | |||
| Yes |
23
3.1%
|
56
3.8%
|
79
3.5%
|
| No |
719
96.9%
|
1432
96.2%
|
2151
96.5%
|
| History of diabetes (Count of Participants) | |||
| Yes |
212
28.6%
|
425
28.6%
|
637
28.6%
|
| No |
530
71.4%
|
1063
71.4%
|
1593
71.4%
|
| History of hypertension (Count of Participants) | |||
| Yes |
594
80.1%
|
1174
78.9%
|
1768
79.3%
|
| No |
148
19.9%
|
314
21.1%
|
462
20.7%
|
| Concomitant lipid-modifying therapy (LMT): Statin (Count of Participants) | |||
| Yes |
742
100%
|
1485
99.8%
|
2227
99.9%
|
| No |
0
0%
|
3
0.2%
|
3
0.1%
|
| Concomitant LMT: Ezetimibe (Count of Participants) | |||
| Yes |
56
7.5%
|
116
7.8%
|
172
7.7%
|
| No |
686
92.5%
|
1372
92.2%
|
2058
92.3%
|
| Concomitant LMT: Fibrate (Count of Participants) | |||
| Yes |
26
3.5%
|
54
3.6%
|
80
3.6%
|
| No |
716
96.5%
|
1434
96.4%
|
2150
96.4%
|
| Concomitant LMT: None (Count of Participants) | |||
| Concomitant LMT: None |
0
0%
|
2
0.1%
|
2
0.1%
|
| Concomitant LMT: Yes |
742
100%
|
1486
99.9%
|
2228
99.9%
|
| Baseline statin intensity (Count of Participants) | |||
| Low |
48
6.5%
|
100
6.7%
|
148
6.6%
|
| Moderate |
324
43.7%
|
646
43.4%
|
970
43.5%
|
| High |
370
49.9%
|
742
49.9%
|
1112
49.9%
|
| Estimated glomerular filtration rate (eGFR) (Count of Participants) | |||
| Normal: ≥ 90 mL/min/1.73m^2 |
167
22.5%
|
320
21.5%
|
487
21.8%
|
| Mild Renal Impairment: 60-89 mL/min/1.73m^2 |
468
63.1%
|
946
63.6%
|
1414
63.4%
|
| Moderate Renal Impairment: 30-59 mL/min/1.73m^2 |
107
14.4%
|
222
14.9%
|
329
14.8%
|
| Total cholesterol (TC) (mg/dL) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mg/dL] |
178.64
(35.645)
|
179.66
(35.143)
|
179.32
(35.306)
|
| Low-density lipoprotein cholesterol (LDL-C) (mg/dL) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mg/dL] |
102.30
(30.048)
|
103.60
(29.127)
|
103.16
(29.436)
|
| High-density lipoprotein cholesterol (HDL-C) (mg/dL) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mg/dL] |
49.29
(11.545)
|
48.71
(11.853)
|
48.90
(11.752)
|
| Triglycerides (TG) (mg/dL) [Median (Inter-Quartile Range) ] | |||
| Median (Inter-Quartile Range) [mg/dL] |
122.50
|
126.25
|
125.00
|
| Non-high-density lipoprotein cholesterol (non-HDL-C) (mg/dL) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mg/dL] |
129.37
(33.855)
|
130.92
(33.677)
|
130.41
(33.737)
|
| Apolipoprotein B (apoB) (mg/dL) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mg/dL] |
86.8
(21.82)
|
88.5
(21.57)
|
87.9
(21.66)
|
| High-sensitivity C-reactive protein (hsCRP) (mg/L) [Median (Inter-Quartile Range) ] | |||
| Median (Inter-Quartile Range) [mg/L] |
1.51
|
1.49
|
1.49
|
Outcome Measures
| Title | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) |
|---|---|
| Description | TEAEs, defined as adverse events (AEs) that began or worsened in severity after the first dose of double-blind study drug and up to 30 days after receiving the last dose of double-blind study drug, were collected and reported. |
| Time Frame | Up to approximately 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all randomized participants who received at least 1 dose of investigational medicinal product. Participants were included in the treatment group that they received, regardless of their randomized treatment. |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 742 | 1487 |
| Any TEAE |
78.7
10.6%
|
78.5
5.3%
|
| Any serious TEAE |
14.0
1.9%
|
14.5
1%
|
| Any fatal TEAE |
0.3
0%
|
0.9
0.1%
|
| Any TEAE leading to discontinuation of study drug |
7.1
1%
|
10.9
0.7%
|
| Title | Percentage of Participants With Adjudicated Major Adverse Cardiovascular Event |
|---|---|
| Description | TEAEs, defined as AEs that began or worsened in severity after the first dose of double-blind study drug and up to 30 days after receiving the last dose of double-blind study drug, were collected and reported. Cardiovascular events were considered as adverse events of special interest. Treatment-emergent = TE. |
| Time Frame | Up to approximately 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 742 | 1487 |
| Any adjudicated major clinical event |
5.7
0.8%
|
4.6
0.3%
|
| Any TE death from cardiovascular causes |
0.1
0%
|
0.4
0%
|
| Any nonfatal myocardial infarction |
1.8
0.2%
|
1.3
0.1%
|
| Any nonfatal stroke |
0.3
0%
|
0.3
0%
|
| Any coronary revascularization |
3.2
0.4%
|
2.6
0.2%
|
| Any hospitalization for unstable angina |
1.5
0.2%
|
0.9
0.1%
|
| TE death from noncardiovascular causes |
0.1
0%
|
0.1
0%
|
| Noncoronary arterial revascularization |
0.8
0.1%
|
0.3
0%
|
| Hospitalization for heart failure |
0.1
0%
|
0.6
0%
|
| Title | Percentage of Participants With the Indicated Event of Special Interest: Creatine Kinase Elevations |
|---|---|
| Description | TEAEs of special interest (AESIs) were predefined and monitored throughout the study. Creatine kinase elevations were assessed using the following preferred term: Blood creatine phosphokinase increased (system organ class: investigations). |
| Time Frame | Up to approximately 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 742 | 1487 |
| Number [percentage of participants] |
1.8
0.2%
|
2.4
0.2%
|
| Title | Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders |
|---|---|
| Description | Treatment-emergent AESIs were predefined and monitored throughout the study. TEAEs potentially related to hepatic events were assessed using the following preferred terms and laboratory abnormalities: aspartate aminotransferase (AST) increased, Alanine aminotransferase (ALT) increased, Hepatic enzyme increased, Blood bilirubin increased, liver function test (LFT) abnormal, LFT increased, hepatic enzyme abnormal, transaminases increased, potential Hy's Law cases (PHLC) [AST and (&)/or ALT >3 x upper limit of normal (ULN) with concurrent total bilirubin >2 x ULN], AST and/or ALT >3 x ULN, and total bilirubin >2 x ULN (system organ class: investigations). AST and ALT values were repeated and confirmed. "Repeated and confirmed" was defined as a participant having the last on-study LFT > x ULN, the last on-treatment LFT > x ULN, or LFT > x ULN followed by another LFT > x ULN. |
| Time Frame | Up to approximately 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population. The percentage of unique participants is reported in the "Overall hepatic disorder AESIs" category; a participant could have been represented in more than one of the individual hepatic disorder AESIs. |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 742 | 1487 |
| Overall hepatic disorder AESIs |
1.5
0.2%
|
2.5
0.2%
|
| AST increased |
0.4
0.1%
|
1.5
0.1%
|
| ALT increased |
0.3
0%
|
0.8
0.1%
|
| Hepatic enzyme increased |
0.0
0%
|
0.5
0%
|
| Blood bilirubin increased |
0.4
0.1%
|
0.1
0%
|
| Liver function test abnormal |
0.3
0%
|
0.1
0%
|
| Liver function test increased |
0.1
0%
|
0.2
0%
|
| Hepatic enzyme abnormal |
0.0
0%
|
0.1
0%
|
| Transaminases increased |
0.1
0%
|
0.0
0%
|
| PHLC [AST &/or ALT>3 x ULN, concurrent TB>2 x ULN] |
0.0
0%
|
0.0
0%
|
| AST and/or ALT >3 x ULN |
0.1
0%
|
0.5
0%
|
| Total bilirubin >2 x ULN |
0.0
0%
|
0.0
0%
|
| Title | Percentage of Participants With the Indicated Event of Special Interest: Hypoglycemia |
|---|---|
| Description | Treatment-emergent AESIs were predefined and monitored throughout the study. Hypoglycemia was assessed using the following preferred terms: hypoglycaemia (system organ class: metabolism and nutrition disorders); blood glucose abnormal and blood glucose decreased (system organ class: investigations). The percentage of unique participants is reported in the "Overall hypoglycemia AESIs" category; a participant could have been represented in more than one of the individual hypoglycemia AESIs. |
| Time Frame | Up to approximately 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 742 | 1487 |
| Overall hypoglycemia AESIs |
3.1
0.4%
|
2.2
0.1%
|
| Hypoglycaemia |
3.0
0.4%
|
2.2
0.1%
|
| Blood glucose abnormal |
0.1
0%
|
0.1
0%
|
| Blood glucose decreased |
0.0
0%
|
0.1
0%
|
| Title | Percentage of Participants With the Indicated Event of Special Interest: Metabolic Acidosis |
|---|---|
| Description | Treatment-emergent AESIs were predefined and monitored throughout the study. Metabolic acidosis was assessed using the preferred term metabolic acidosis (system organ class: metabolism and nutrition disorders). |
| Time Frame | Up to approximately 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 742 | 1487 |
| Number [percentage of participants] |
0.0
0%
|
0.1
0%
|
| Title | Percentage of Participants With the Indicated Event of Special Interest: Muscular Disorder |
|---|---|
| Description | Treatment-emergent AESIs were predefined and monitored throughout the study. Muscular safety was assessed using the following preferred terms and laboratory abnormalities: myalgia, muscle spasms, pain in extremity, muscular weakness (system organ class: musculoskeletal and connective tissue disorders), and creatine kinase >5 ULN (repeated and confirmed). The percentage of unique participants is reported in the "Overall muscular disorder AESIs" category; a participant could have been represented in more than one of the individual muscular disorder AESIs. |
| Time Frame | Up to approximately 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 742 | 1487 |
| Overall muscular disorder AESIs |
10.1
1.4%
|
13.1
0.9%
|
| Myalgia |
6.1
0.8%
|
6.0
0.4%
|
| Muscle spasms |
2.7
0.4%
|
4.2
0.3%
|
| Pain in extremity |
2.2
0.3%
|
3.4
0.2%
|
| Muscular weakness |
0.5
0.1%
|
0.6
0%
|
| Creatine kinase >5 ULN |
0.1
0%
|
0.5
0%
|
| Title | Percentage of Participants With the Indicated Event of Special Interest: Neurocognitive Disorder |
|---|---|
| Description | Treatment-emergent AESIs were predefined and monitored throughout the study. Neurocognitive disorder was assessed using the following preferred terms: memory impairment, amnesia, and cognitive disorder (system organ class: nervous system disorders); confusional state and disorientation (system organ class: psychiatric disorders). The percentage of unique participants is reported in the "Overall neurocognitive disorder AESIs" category; a participant could have been represented in more than one of the individual neurocognitive disorder AESIs. |
| Time Frame | Up to approximately 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 742 | 1487 |
| Overall neurocognitive disorder AESIs |
0.9
0.1%
|
0.7
0%
|
| Memory impairment |
0.5
0.1%
|
0.3
0%
|
| Amnesia |
0.4
0.1%
|
0.2
0%
|
| Cognitive disorder |
0.0
0%
|
0.1
0%
|
| Confusional state |
0.0
0%
|
0.1
0%
|
| Disorientation |
0.0
0%
|
0.1
0%
|
| Title | Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus |
|---|---|
| Description | Treatment-emergent AESIs were predefined and monitored throughout the study. New onset or worsening diabetes was assessed using the following preferred terms: type 2 diabetes mellitus, diabetes mellitus, hyperglycaemia, glucose tolerance impaired, diabetes mellitus inadequate control, and impaired fasting glucose (system organ class: metabolism and nutrition disorders); blood glucose increased, glycosylated haemoglobin increased, blood glucose abnormal, and glucose urine present (system organ class: investigations); and glycosuria (system organ class: renal and urinary disorders). The percentage of unique participants is reported in the "Overall new onset/worsening diabetes mellitus AESIs" category; a participant could have been represented in more than one of the individual new onset/worsening diabetes mellitus AESIs. |
| Time Frame | Up to approximately 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 742 | 1487 |
| Overall new onset/worsening diabetes mellitus AESI |
5.4
0.7%
|
3.3
0.2%
|
| Type 2 diabetes mellitus |
0.9
0.1%
|
1.0
0.1%
|
| Diabetes mellitus |
0.9
0.1%
|
0.4
0%
|
| Hyperglycaemia |
0.7
0.1%
|
0.5
0%
|
| Glucose tolerance impaired |
0.1
0%
|
0.4
0%
|
| Diabetes mellitus inadequate control |
0.4
0.1%
|
0.1
0%
|
| Impaired fasting glucose |
0.3
0%
|
0.1
0%
|
| Blood glucose increased |
1.2
0.2%
|
0.7
0%
|
| Glycosylated haemoglobin increased |
0.5
0.1%
|
0.0
0%
|
| Blood glucose abnormal |
0.1
0%
|
0.1
0%
|
| Glucose urine present |
0.1
0%
|
0.0
0%
|
| Glycosuria |
0.3
0%
|
0.1
0%
|
| Title | Percentage of Participants With the Indicated Event of Special Interest: Renal Disorder |
|---|---|
| Description | Treatment-emergent AESIs were predefined and monitored throughout the study. TEAEs potentially related to renal events were assessed using the following preferred terms: renal failure, renal impairment, acute kidney injury (system organ class: renal and urinary disorders); blood creatinine increased, glomerular filtration rate decreased, blood urea increased, estimated glomerular filtration rate (eGFR) <30 milliliter per minute per 1.73 square meter (ml/min/1.73m^2), and change from baseline in creatinine >1 mg/dL (system organ class: investigations); and gout (system organ class: metabolism and nutrition disorders). The percentage of unique participants is reported in the "Overall renal disorder AESIs" category; a participant could have been represented in more than one of the individual renal disorder AESIs. |
| Time Frame | Up to approximately 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 742 | 1487 |
| Renal failure |
0.1
0%
|
0.9
0.1%
|
| Renal impairment |
0.1
0%
|
0.4
0%
|
| Acute kidney injury |
0.3
0%
|
0.3
0%
|
| Blood creatinine increased |
0.4
0.1%
|
0.8
0.1%
|
| Glomerular filtration rate decreased |
0.0
0%
|
0.5
0%
|
| Blood urea increased |
0.1
0%
|
0.1
0%
|
| Gout |
0.3
0%
|
1.2
0.1%
|
| Change from baseline in creatinine >1 mg/dL |
0.0
0%
|
0.1
0%
|
| eGFR <30 mL/min/1.73 m^2 |
0.4
0.1%
|
0.9
0.1%
|
| Title | Change From Baseline to Week 52 in Uric Acid (Urate) Level |
|---|---|
| Description | Blood samples were drawn at defined time points during the course of the study to monitor uric acid (urate) levels. |
| Time Frame | Baseline and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population. Only participants with available data were analyzed. |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 742 | 1487 |
| Baseline |
5.96
(1.35)
|
6.06
(1.37)
|
| Change from Baseline at Week 52 |
-0.06
(0.87)
|
0.73
(1.11)
|
| Title | Change From Baseline to Week 52 in Creatinine Level |
|---|---|
| Description | Blood samples were drawn at defined time points during the course of the study to monitor creatinine levels. |
| Time Frame | Baseline and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population. Only participants with available data were analyzed. |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 742 | 1487 |
| Baseline |
0.96
(0.22)
|
0.97
(0.22)
|
| Change from Baseline at Week 52 |
-0.02
(0.12)
|
0.02
(0.13)
|
| Title | Change From Baseline to Week 52 in Hemoglobin Level |
|---|---|
| Description | Blood samples were drawn at defined time points during the course of the study to monitor hemoglobin levels. |
| Time Frame | Baseline and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population. Only participants with available data were analyzed. |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 742 | 1487 |
| Baseline |
14.07
(1.26)
|
14.22
(1.26)
|
| Change from Baseline at Week 52 |
-0.23
(0.85)
|
-0.58
(0.88)
|
| Title | Percent Change From Baseline to Week 12 in Low-density Lipoprotein Cholesterol (LDL-C) |
|---|---|
| Description | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: [(LDL-C value at Week 12 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen. Least Square mean= LS mean. Percent change was analyzed using the analysis of covariance (ANCOVA) method, which included treatment, randomization stratum as factors, and baseline value as covariate. |
| Time Frame | Baseline; Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all randomized participants |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 742 | 1488 |
| Least Squares Mean (Standard Error) [percent change] |
1.6
(0.86)
|
-16.5
(0.52)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Bempedoic Acid |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in LS mean |
| Estimated Value | -18.1 | |
| Confidence Interval |
(2-Sided) 95% -20 to -16.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.01 |
|
| Estimation Comments | ||
| Title | Absolute Change From Baseline to Week 12 in LDL-C |
|---|---|
| Description | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Absolute change from baseline was calculated as: LDL-C value at Week 12 minus Baseline value. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen. |
| Time Frame | Baseline; Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set. Only participants with available data were analyzed. |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 725 | 1424 |
| Mean (Standard Deviation) [mg/dL] |
0.43
(27.04)
|
-19.23
(24.01)
|
| Title | Percent Change From Baseline to Week 24 in LDL-C |
|---|---|
| Description | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: [(LDL-C value at Week 24 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate. |
| Time Frame | Baseline; Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 742 | 1488 |
| Least Squares Mean (Standard Error) [percent change] |
1.2
(0.88)
|
-14.9
(0.60)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Bempedoic Acid |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in LS mean |
| Estimated Value | -16.1 | |
| Confidence Interval |
(2-Sided) 95% -18.2 to -14 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.07 |
|
| Estimation Comments | ||
| Title | Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) |
|---|---|
| Description | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for non-HDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: [(non-HDL-C value at Week 12 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate. |
| Time Frame | Baseline; Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 742 | 1488 |
| Least Squares Mean (Standard Error) [percent change] |
1.5
(0.76)
|
-11.9
(0.48)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Bempedoic Acid |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in LS mean |
| Estimated Value | -13.3 | |
| Confidence Interval |
(2-Sided) 95% -15.1 to -11.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.9 |
|
| Estimation Comments | ||
| Title | Percent Change From Baseline to Week 12 in Total Cholesterol (TC) |
|---|---|
| Description | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for TC. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: [(TC value at Week 12 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate. |
| Time Frame | Baseline; Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 742 | 1488 |
| Least Squares Mean (Standard Error) [percent change] |
0.8
(0.57)
|
-10.3
(0.37)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Bempedoic Acid |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in LS mean |
| Estimated Value | -11.1 | |
| Confidence Interval |
(2-Sided) 95% -12.5 to -9.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.69 |
|
| Estimation Comments | ||
| Title | Percent Change From Baseline to Week 12 in Apolipoprotein B (apoB) |
|---|---|
| Description | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for apoB. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: [(apoB value at Week 12 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate. |
| Time Frame | Baseline; Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set. Only participants with available data were analyzed. |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 736 | 1485 |
| Least Squares Mean (Standard Error) [percent change] |
3.3
(0.70)
|
-8.6
(0.47)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Bempedoic Acid |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in LS mean |
| Estimated Value | -11.9 | |
| Confidence Interval |
(2-Sided) 95% -13.6 to -10.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.85 |
|
| Estimation Comments | ||
| Title | Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP) |
|---|---|
| Description | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for hsCRP. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: [(hsCRP value at Week 12 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate. |
| Time Frame | Baseline; Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set. Only participants with available data were analyzed. |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 724 | 1421 |
| Least Squares Mean (Standard Error) [percent change] |
2.6
(91.9)
|
-22.4
(72.5)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Bempedoic Acid |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Location shift |
| Estimated Value | -21.5 | |
| Confidence Interval |
(2-Sided) 95% -26.96 to -16 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.8 |
|
| Estimation Comments | ||
| Title | Percent Change From Baseline to Week 52 in LDL-C |
|---|---|
| Description | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: [(LDL-C value at Week 52 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate. |
| Time Frame | Baseline; Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set. Only participants with available data were analyzed. |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 685 | 1364 |
| Least Squares Mean (Standard Error) [percent change] |
1.0
(0.92)
|
-12.6
(0.66)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Bempedoic Acid |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in LS mean |
| Estimated Value | -13.6 | |
| Confidence Interval |
(2-Sided) 95% -15.8 to -11.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.13 |
|
| Estimation Comments | ||
| Title | Percent Change From Baseline to Week 24 in Non-HDL-C |
|---|---|
| Description | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for non-HDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: [(non-HDL-C value at Week 24 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed. |
| Time Frame | Baseline; Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set. Only participants with available data were analyzed. |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 707 | 1396 |
| Mean (Standard Deviation) [percent change] |
1.61
(20.91)
|
-11.69
(19.80)
|
| Title | Percent Change From Baseline to Week 52 in Non-HDL-C |
|---|---|
| Description | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for non-HDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: [(non-HDL-C value at Week 52 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed. |
| Time Frame | Baseline; Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set. Only participants with available data were analyzed. |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 685 | 1364 |
| Mean (Standard Deviation) [percent change] |
0.65
(21.438)
|
-10.07
(22.097)
|
| Title | Percent Change From Baseline to Week 24 in TC |
|---|---|
| Description | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for TC. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: [(TC value at Week 24 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed. |
| Time Frame | Baseline; Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set. Only participants with available data were analyzed. |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 708 | 1396 |
| Mean (Standard Deviation) [percent change] |
1.15
(15.349)
|
-9.86
(15.358)
|
| Title | Percent Change From Baseline to Week 52 in TC |
|---|---|
| Description | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for TC. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: [(TC value at Week 52 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed. |
| Time Frame | Baseline; Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set. Only participants with available data were analyzed. |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 685 | 1365 |
| Mean (Standard Deviation) [percent change] |
0.38
(16.180)
|
-8.92
(16.945)
|
| Title | Percent Change From Baseline to Week 24 in apoB |
|---|---|
| Description | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for apoB. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: [(apoB value at Week 24 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed |
| Time Frame | Baseline; Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set. Only participants with available data were analyzed. |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 699 | 1381 |
| Mean (Standard Deviation) [percent change] |
4.8
(20.41)
|
-7.1
(20.01)
|
| Title | Percent Change From Baseline to Week 52 in apoB |
|---|---|
| Description | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for apoB. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: [(apoB value at Week 52 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed. |
| Time Frame | Baseline; Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set. Only participants with available data were analyzed. |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 676 | 1342 |
| Mean (Standard Deviation) [percent change] |
3.4
(20.24)
|
-6.0
(22.54)
|
| Title | Percent Change From Baseline to Week 24 in hsCRP |
|---|---|
| Description | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for hsCRP. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: [(hsCRP value at Week 24 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed. |
| Time Frame | Baseline; Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set. Only participants with available data were analyzed. |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 706 | 1392 |
| Median (Inter-Quartile Range) [percent change] |
2.727
|
-16.382
|
| Title | Percent Change From Baseline to Week 52 in hsCRP |
|---|---|
| Description | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for hsCRP. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: [(hsCRP value at Week 52 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed. |
| Time Frame | Baseline; Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set. Only participants with available data were analyzed. |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 681 | 1358 |
| Median (Inter-Quartile Range) [percent change] |
1.818
|
-14.445
|
| Title | Percentage of Participants Achieving LDL-C <70 mg/dL at Week 12, 24, and 52 |
|---|---|
| Description | The percentage of participants who achieved lowering in lipid values of LDL-C below 70 mg/dL have been reported. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Observed data was used for the analysis, no imputation for the missing data was performed. |
| Time Frame | Week 12, Week 24, and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set. Only participants with available data were analyzed. |
| Arm/Group Title | Placebo | Bempedoic Acid |
|---|---|---|
| Arm/Group Description | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. |
| Measure Participants | 742 | 1488 |
| Week 12 |
9.0
1.2%
|
32.4
2.2%
|
| Week 24 |
10.2
1.4%
|
32.0
2.2%
|
| Week 52 |
9.5
1.3%
|
28.2
1.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Bempedoic Acid |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Chi-squared | |
| Comments | ||
Adverse Events
| Time Frame | Up to approximately 52 weeks | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of double-blind study drug and up to 30 days after receiving the last dose of double-blind study drug, were collected and reported. | |||
| Arm/Group Title | Bempedoic Acid | Placebo | ||
| Arm/Group Description | During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | ||
All Cause Mortality |
||||
| Bempedoic Acid | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 13/1487 (0.9%) | 2/742 (0.3%) | ||
Serious Adverse Events |
||||
| Bempedoic Acid | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 216/1487 (14.5%) | 104/742 (14%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 2/1487 (0.1%) | 1/742 (0.1%) | ||
| Cardiac disorders | ||||
| Acute left ventricular failure | 1/1487 (0.1%) | 0/742 (0%) | ||
| Acute coronary syndrome | 0/1487 (0%) | 2/742 (0.3%) | ||
| Acute myocardial infarction | 11/1487 (0.7%) | 5/742 (0.7%) | ||
| Angina pectoris | 11/1487 (0.7%) | 6/742 (0.8%) | ||
| Angina unstable | 18/1487 (1.2%) | 12/742 (1.6%) | ||
| Aortic valve incompetence | 1/1487 (0.1%) | 0/742 (0%) | ||
| Arrhythmia | 0/1487 (0%) | 1/742 (0.1%) | ||
| Atrial fibrillation | 7/1487 (0.5%) | 1/742 (0.1%) | ||
| Arteriospasm coronary | 1/1487 (0.1%) | 0/742 (0%) | ||
| Atrial flutter | 1/1487 (0.1%) | 2/742 (0.3%) | ||
| Atrial tachycardia | 1/1487 (0.1%) | 0/742 (0%) | ||
| Atrioventricular block complete | 0/1487 (0%) | 1/742 (0.1%) | ||
| Atrioventricular block second degree | 1/1487 (0.1%) | 0/742 (0%) | ||
| Cardiac arrest | 1/1487 (0.1%) | 1/742 (0.1%) | ||
| Bradycardia | 2/1487 (0.1%) | 0/742 (0%) | ||
| Cardiac failure | 5/1487 (0.3%) | 3/742 (0.4%) | ||
| Cardiac failure acute | 0/1487 (0%) | 1/742 (0.1%) | ||
| Cardiac failure congestive | 4/1487 (0.3%) | 1/742 (0.1%) | ||
| Coronary artery disease | 9/1487 (0.6%) | 6/742 (0.8%) | ||
| Hypertensive heart disease | 1/1487 (0.1%) | 0/742 (0%) | ||
| Ischaemic cardiomyopathy | 1/1487 (0.1%) | 0/742 (0%) | ||
| Left ventricular dilatation | 1/1487 (0.1%) | 0/742 (0%) | ||
| Myocardial ischaemia | 4/1487 (0.3%) | 1/742 (0.1%) | ||
| Myocardial infarction | 8/1487 (0.5%) | 5/742 (0.7%) | ||
| Pericarditis | 2/1487 (0.1%) | 0/742 (0%) | ||
| Sinus node dysfunction | 2/1487 (0.1%) | 0/742 (0%) | ||
| Supraventricular tachycardia | 2/1487 (0.1%) | 0/742 (0%) | ||
| Ventricular fibrillation | 2/1487 (0.1%) | 1/742 (0.1%) | ||
| Ventricular tachycardia | 2/1487 (0.1%) | 1/742 (0.1%) | ||
| Left ventricular failure | 1/1487 (0.1%) | 0/742 (0%) | ||
| Congenital, familial and genetic disorders | ||||
| Myotonic dystrophy | 1/1487 (0.1%) | 0/742 (0%) | ||
| Endocrine disorders | ||||
| Goitre | 1/1487 (0.1%) | 0/742 (0%) | ||
| Hyperparathyroidism primary | 1/1487 (0.1%) | 0/742 (0%) | ||
| Eye disorders | ||||
| Retinal detachment | 1/1487 (0.1%) | 0/742 (0%) | ||
| Cataract | 1/1487 (0.1%) | 1/742 (0.1%) | ||
| Gastrointestinal disorders | ||||
| Constipation | 1/1487 (0.1%) | 0/742 (0%) | ||
| Abdominal hernia | 1/1487 (0.1%) | 0/742 (0%) | ||
| Diarrhoea | 1/1487 (0.1%) | 0/742 (0%) | ||
| Diverticular perforation | 0/1487 (0%) | 1/742 (0.1%) | ||
| Duodenal ulcer | 0/1487 (0%) | 1/742 (0.1%) | ||
| Enteritis | 0/1487 (0%) | 1/742 (0.1%) | ||
| Gastritis | 2/1487 (0.1%) | 0/742 (0%) | ||
| Gastrointestinal haemorrhage | 1/1487 (0.1%) | 0/742 (0%) | ||
| Inguinal hernia | 1/1487 (0.1%) | 1/742 (0.1%) | ||
| Internal hernia | 1/1487 (0.1%) | 0/742 (0%) | ||
| Large intestine polyp | 1/1487 (0.1%) | 0/742 (0%) | ||
| Mallory-Weiss syndrome | 1/1487 (0.1%) | 0/742 (0%) | ||
| Obstructive pancreatitis | 1/1487 (0.1%) | 1/742 (0.1%) | ||
| Pancreatitis acute | 2/1487 (0.1%) | 0/742 (0%) | ||
| Pancreatic pseudocyst | 1/1487 (0.1%) | 0/742 (0%) | ||
| Rectal haemorrhage | 0/1487 (0%) | 1/742 (0.1%) | ||
| Pancreatitis relapsing | 1/1487 (0.1%) | 0/742 (0%) | ||
| Umbilical hernia | 1/1487 (0.1%) | 1/742 (0.1%) | ||
| Small intestinal obstruction | 0/1487 (0%) | 1/742 (0.1%) | ||
| Upper gastrointestinal haemorrhage | 1/1487 (0.1%) | 1/742 (0.1%) | ||
| Abdominal pain | 1/1487 (0.1%) | 0/742 (0%) | ||
| General disorders | ||||
| Asthenia | 1/1487 (0.1%) | 1/742 (0.1%) | ||
| Chest discomfort | 1/1487 (0.1%) | 1/742 (0.1%) | ||
| Chest pain | 1/1487 (0.1%) | 1/742 (0.1%) | ||
| Death | 0/1487 (0%) | 1/742 (0.1%) | ||
| Eye complication associated with device | 0/1487 (0%) | 1/742 (0.1%) | ||
| Granuloma | 1/1487 (0.1%) | 0/742 (0%) | ||
| Gait disturbance | 1/1487 (0.1%) | 0/742 (0%) | ||
| Hernia | 1/1487 (0.1%) | 0/742 (0%) | ||
| Multiple organ dysfunction syndrome | 1/1487 (0.1%) | 0/742 (0%) | ||
| Pelvic mass | 0/1487 (0%) | 1/742 (0.1%) | ||
| Non-cardiac chest pain | 7/1487 (0.5%) | 4/742 (0.5%) | ||
| Vascular stent restenosis | 1/1487 (0.1%) | 0/742 (0%) | ||
| Hepatobiliary disorders | ||||
| Cholecystitis acute | 0/1487 (0%) | 1/742 (0.1%) | ||
| Cholecystitis | 3/1487 (0.2%) | 0/742 (0%) | ||
| Cholelithiasis | 3/1487 (0.2%) | 1/742 (0.1%) | ||
| Jaundice | 1/1487 (0.1%) | 0/742 (0%) | ||
| Portal vein thrombosis | 1/1487 (0.1%) | 0/742 (0%) | ||
| Immune system disorders | ||||
| Immune system disorder | 1/1487 (0.1%) | 0/742 (0%) | ||
| Infections and infestations | ||||
| Abscess jaw | 0/1487 (0%) | 1/742 (0.1%) | ||
| Abdominal sepsis | 1/1487 (0.1%) | 0/742 (0%) | ||
| Appendicitis | 1/1487 (0.1%) | 0/742 (0%) | ||
| Bronchitis | 1/1487 (0.1%) | 1/742 (0.1%) | ||
| Campylobacter gastroenteritis | 1/1487 (0.1%) | 0/742 (0%) | ||
| Clostridium difficile infection | 1/1487 (0.1%) | 0/742 (0%) | ||
| Cellulitis | 2/1487 (0.1%) | 0/742 (0%) | ||
| Erysipelas | 3/1487 (0.2%) | 0/742 (0%) | ||
| Diverticulitis | 4/1487 (0.3%) | 0/742 (0%) | ||
| Gastroenteritis | 1/1487 (0.1%) | 0/742 (0%) | ||
| Helicobacter infection | 0/1487 (0%) | 1/742 (0.1%) | ||
| Implant site infection | 0/1487 (0%) | 1/742 (0.1%) | ||
| Infected bite | 1/1487 (0.1%) | 0/742 (0%) | ||
| Infective aneurysm | 1/1487 (0.1%) | 0/742 (0%) | ||
| Influenza | 2/1487 (0.1%) | 0/742 (0%) | ||
| Localised infection | 1/1487 (0.1%) | 0/742 (0%) | ||
| Medical device site joint infection | 1/1487 (0.1%) | 0/742 (0%) | ||
| Pneumonia | 6/1487 (0.4%) | 1/742 (0.1%) | ||
| Peritonitis | 0/1487 (0%) | 1/742 (0.1%) | ||
| Pulmonary sepsis | 1/1487 (0.1%) | 0/742 (0%) | ||
| Pyelonephritis | 2/1487 (0.1%) | 0/742 (0%) | ||
| Respiratory tract infection | 1/1487 (0.1%) | 0/742 (0%) | ||
| Salmonella bacteraemia | 1/1487 (0.1%) | 0/742 (0%) | ||
| Sepsis | 1/1487 (0.1%) | 1/742 (0.1%) | ||
| Skin infection | 1/1487 (0.1%) | 0/742 (0%) | ||
| Septic shock | 1/1487 (0.1%) | 1/742 (0.1%) | ||
| Staphylococcal osteomyelitis | 1/1487 (0.1%) | 0/742 (0%) | ||
| Tonsillitis bacterial | 1/1487 (0.1%) | 0/742 (0%) | ||
| Urinary tract infection | 2/1487 (0.1%) | 1/742 (0.1%) | ||
| Viral infection | 1/1487 (0.1%) | 0/742 (0%) | ||
| Wound infection | 1/1487 (0.1%) | 0/742 (0%) | ||
| Gastroenteritis viral | 0/1487 (0%) | 1/742 (0.1%) | ||
| Enteritis necroticans | 0/1487 (0%) | 1/742 (0.1%) | ||
| Infective exacerbation of chronic obstructive airways disease | 0/1487 (0%) | 1/742 (0.1%) | ||
| Injury, poisoning and procedural complications | ||||
| Anaemia postoperative | 1/1487 (0.1%) | 1/742 (0.1%) | ||
| Alcohol poisoning | 0/1487 (0%) | 1/742 (0.1%) | ||
| Cardiac function disturbance postoperative | 0/1487 (0%) | 1/742 (0.1%) | ||
| Arterial injury | 1/1487 (0.1%) | 0/742 (0%) | ||
| Facial bones fracture | 2/1487 (0.1%) | 0/742 (0%) | ||
| Fall | 1/1487 (0.1%) | 0/742 (0%) | ||
| Femur fracture | 1/1487 (0.1%) | 0/742 (0%) | ||
| Foreign body | 1/1487 (0.1%) | 0/742 (0%) | ||
| Head injury | 0/1487 (0%) | 1/742 (0.1%) | ||
| Hip fracture | 0/1487 (0%) | 1/742 (0.1%) | ||
| Humerus fracture | 1/1487 (0.1%) | 1/742 (0.1%) | ||
| Incisional hernia | 1/1487 (0.1%) | 0/742 (0%) | ||
| Multiple injuries | 1/1487 (0.1%) | 0/742 (0%) | ||
| Radius fracture | 2/1487 (0.1%) | 0/742 (0%) | ||
| Post procedural haemorrhage | 1/1487 (0.1%) | 1/742 (0.1%) | ||
| Road traffic accident | 0/1487 (0%) | 1/742 (0.1%) | ||
| Scapula fracture | 1/1487 (0.1%) | 0/742 (0%) | ||
| Subarachnoid haemorrhage | 1/1487 (0.1%) | 0/742 (0%) | ||
| Subdural haemorrhage | 1/1487 (0.1%) | 0/742 (0%) | ||
| Thoracic vertebral fracture | 1/1487 (0.1%) | 0/742 (0%) | ||
| Vascular graft thrombosis | 1/1487 (0.1%) | 0/742 (0%) | ||
| Tendon rupture | 1/1487 (0.1%) | 0/742 (0%) | ||
| Investigations | ||||
| Blood pressure increased | 1/1487 (0.1%) | 0/742 (0%) | ||
| Liver function test abnormal | 1/1487 (0.1%) | 0/742 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Diabetes mellitus | 0/1487 (0%) | 1/742 (0.1%) | ||
| Diabetes mellitus inadequate control | 0/1487 (0%) | 1/742 (0.1%) | ||
| Gout | 1/1487 (0.1%) | 0/742 (0%) | ||
| Hypercalcaemia | 0/1487 (0%) | 1/742 (0.1%) | ||
| Hyperkalaemia | 2/1487 (0.1%) | 0/742 (0%) | ||
| Hyponatraemia | 0/1487 (0%) | 1/742 (0.1%) | ||
| Type 2 diabetes mellitus | 1/1487 (0.1%) | 0/742 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 1/1487 (0.1%) | 1/742 (0.1%) | ||
| Arthritis | 1/1487 (0.1%) | 0/742 (0%) | ||
| Foot deformity | 1/1487 (0.1%) | 0/742 (0%) | ||
| Back pain | 1/1487 (0.1%) | 0/742 (0%) | ||
| Intervertebral disc compression | 1/1487 (0.1%) | 0/742 (0%) | ||
| Intervertebral disc protrusion | 2/1487 (0.1%) | 1/742 (0.1%) | ||
| Intervertebral disc degeneration | 1/1487 (0.1%) | 0/742 (0%) | ||
| Musculoskeletal pain | 1/1487 (0.1%) | 0/742 (0%) | ||
| Lumbar spinal stenosis | 1/1487 (0.1%) | 0/742 (0%) | ||
| Osteoarthritis | 0/1487 (0%) | 3/742 (0.4%) | ||
| Myositis | 1/1487 (0.1%) | 0/742 (0%) | ||
| Pain in extremity | 1/1487 (0.1%) | 0/742 (0%) | ||
| Rotator cuff syndrome | 1/1487 (0.1%) | 0/742 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Adenocarcinoma of colon | 2/1487 (0.1%) | 0/742 (0%) | ||
| Bladder cancer | 1/1487 (0.1%) | 1/742 (0.1%) | ||
| Basal cell carcinoma | 0/1487 (0%) | 1/742 (0.1%) | ||
| Brain neoplasm | 1/1487 (0.1%) | 0/742 (0%) | ||
| Bladder neoplasm | 2/1487 (0.1%) | 0/742 (0%) | ||
| Gallbladder cancer | 1/1487 (0.1%) | 0/742 (0%) | ||
| Lung adenocarcinoma | 1/1487 (0.1%) | 0/742 (0%) | ||
| Lung neoplasm malignant | 3/1487 (0.2%) | 0/742 (0%) | ||
| Lung squamous cell carcinoma metastatic | 1/1487 (0.1%) | 0/742 (0%) | ||
| Malignant melanoma | 1/1487 (0.1%) | 0/742 (0%) | ||
| Oropharyngeal cancer | 1/1487 (0.1%) | 0/742 (0%) | ||
| Metastases to liver | 1/1487 (0.1%) | 0/742 (0%) | ||
| Pancreatic carcinoma | 0/1487 (0%) | 1/742 (0.1%) | ||
| Prostate cancer | 3/1487 (0.2%) | 2/742 (0.3%) | ||
| Ureteric cancer | 0/1487 (0%) | 1/742 (0.1%) | ||
| Squamous cell carcinoma of skin | 0/1487 (0%) | 1/742 (0.1%) | ||
| Nervous system disorders | ||||
| Brain oedema | 2/1487 (0.1%) | 0/742 (0%) | ||
| Altered state of consciousness | 1/1487 (0.1%) | 0/742 (0%) | ||
| Carotid artery disease | 2/1487 (0.1%) | 0/742 (0%) | ||
| Carotid artery stenosis | 1/1487 (0.1%) | 1/742 (0.1%) | ||
| Carotid artery occlusion | 0/1487 (0%) | 1/742 (0.1%) | ||
| Cerebrovascular accident | 3/1487 (0.2%) | 2/742 (0.3%) | ||
| Cerebral infarction | 1/1487 (0.1%) | 0/742 (0%) | ||
| Dementia | 1/1487 (0.1%) | 0/742 (0%) | ||
| Cognitive disorder | 1/1487 (0.1%) | 0/742 (0%) | ||
| Dizziness | 1/1487 (0.1%) | 0/742 (0%) | ||
| Headache | 1/1487 (0.1%) | 0/742 (0%) | ||
| Ischaemic stroke | 1/1487 (0.1%) | 0/742 (0%) | ||
| Ischaemic cerebral infarction | 1/1487 (0.1%) | 0/742 (0%) | ||
| Neuralgia | 1/1487 (0.1%) | 0/742 (0%) | ||
| Lumbar radiculopathy | 1/1487 (0.1%) | 0/742 (0%) | ||
| Paraesthesia | 0/1487 (0%) | 1/742 (0.1%) | ||
| Presyncope | 1/1487 (0.1%) | 1/742 (0.1%) | ||
| Reversible ischaemic neurological deficit | 0/1487 (0%) | 1/742 (0.1%) | ||
| Ruptured cerebral aneurysm | 1/1487 (0.1%) | 0/742 (0%) | ||
| Speech disorder | 1/1487 (0.1%) | 0/742 (0%) | ||
| Syncope | 3/1487 (0.2%) | 3/742 (0.4%) | ||
| Transient ischaemic attack | 3/1487 (0.2%) | 2/742 (0.3%) | ||
| Psychiatric disorders | ||||
| Major depression | 0/1487 (0%) | 1/742 (0.1%) | ||
| Intensive care unit delirium | 1/1487 (0.1%) | 0/742 (0%) | ||
| Renal and urinary disorders | ||||
| Acute kidney injury | 1/1487 (0.1%) | 2/742 (0.3%) | ||
| Haematuria | 2/1487 (0.1%) | 1/742 (0.1%) | ||
| Nephrolithiasis | 1/1487 (0.1%) | 1/742 (0.1%) | ||
| Renal colic | 1/1487 (0.1%) | 0/742 (0%) | ||
| Urinary bladder polyp | 1/1487 (0.1%) | 0/742 (0%) | ||
| Reproductive system and breast disorders | ||||
| Benign prostatic hyperplasia | 3/1487 (0.2%) | 1/742 (0.1%) | ||
| Endometrial hyperplasia | 1/1487 (0.1%) | 0/742 (0%) | ||
| Prostatitis | 1/1487 (0.1%) | 0/742 (0%) | ||
| Uterine polyp | 1/1487 (0.1%) | 0/742 (0%) | ||
| Uterine prolapse | 2/1487 (0.1%) | 0/742 (0%) | ||
| Vaginal prolapse | 1/1487 (0.1%) | 0/742 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute pulmonary oedema | 1/1487 (0.1%) | 0/742 (0%) | ||
| Asthma | 1/1487 (0.1%) | 0/742 (0%) | ||
| Acute respiratory failure | 1/1487 (0.1%) | 0/742 (0%) | ||
| Chronic obstructive pulmonary disease | 3/1487 (0.2%) | 2/742 (0.3%) | ||
| Dyspnoea | 2/1487 (0.1%) | 0/742 (0%) | ||
| Eosinophilic pneumonia | 1/1487 (0.1%) | 0/742 (0%) | ||
| Lung cyst | 1/1487 (0.1%) | 0/742 (0%) | ||
| Pleural effusion | 1/1487 (0.1%) | 0/742 (0%) | ||
| Pulmonary embolism | 2/1487 (0.1%) | 1/742 (0.1%) | ||
| Sleep apnoea syndrome | 2/1487 (0.1%) | 0/742 (0%) | ||
| Vascular disorders | ||||
| Aortic aneurysm | 1/1487 (0.1%) | 1/742 (0.1%) | ||
| Aortic stenosis | 2/1487 (0.1%) | 1/742 (0.1%) | ||
| Blood pressure inadequately controlled | 0/1487 (0%) | 1/742 (0.1%) | ||
| Haematoma | 0/1487 (0%) | 1/742 (0.1%) | ||
| Deep vein thrombosis | 2/1487 (0.1%) | 0/742 (0%) | ||
| Hypertension | 1/1487 (0.1%) | 0/742 (0%) | ||
| Hypertensive crisis | 1/1487 (0.1%) | 1/742 (0.1%) | ||
| Hypotension | 0/1487 (0%) | 1/742 (0.1%) | ||
| Orthostatic hypotension | 0/1487 (0%) | 1/742 (0.1%) | ||
| Intermittent claudication | 0/1487 (0%) | 1/742 (0.1%) | ||
| Peripheral arterial occlusive disease | 2/1487 (0.1%) | 3/742 (0.4%) | ||
| Peripheral artery aneurysm | 1/1487 (0.1%) | 0/742 (0%) | ||
| Peripheral artery occlusion | 0/1487 (0%) | 1/742 (0.1%) | ||
| Peripheral artery thrombosis | 0/1487 (0%) | 1/742 (0.1%) | ||
| Peripheral vascular disorder | 1/1487 (0.1%) | 0/742 (0%) | ||
| Peripheral ischaemia | 1/1487 (0.1%) | 0/742 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Bempedoic Acid | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 792/1487 (53.3%) | 381/742 (51.3%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 41/1487 (2.8%) | 15/742 (2%) | ||
| Cardiac disorders | ||||
| Angina pectoris | 24/1487 (1.6%) | 19/742 (2.6%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 43/1487 (2.9%) | 19/742 (2.6%) | ||
| Constipation | 26/1487 (1.7%) | 18/742 (2.4%) | ||
| Diarrhoea | 60/1487 (4%) | 30/742 (4%) | ||
| General disorders | ||||
| Fatigue | 38/1487 (2.6%) | 25/742 (3.4%) | ||
| Infections and infestations | ||||
| Bronchitis | 52/1487 (3.5%) | 19/742 (2.6%) | ||
| Lower respiratory tract infection | 41/1487 (2.8%) | 19/742 (2.6%) | ||
| Sinusitis | 26/1487 (1.7%) | 18/742 (2.4%) | ||
| Nasopharyngitis | 146/1487 (9.8%) | 87/742 (11.7%) | ||
| Urinary tract infection | 70/1487 (4.7%) | 47/742 (6.3%) | ||
| Upper respiratory tract infection | 72/1487 (4.8%) | 31/742 (4.2%) | ||
| Investigations | ||||
| Blood creatine phosphokinase increased | 35/1487 (2.4%) | 13/742 (1.8%) | ||
| Metabolism and nutrition disorders | ||||
| Hypoglycaemia | 32/1487 (2.2%) | 22/742 (3%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 64/1487 (4.3%) | 44/742 (5.9%) | ||
| Back pain | 55/1487 (3.7%) | 18/742 (2.4%) | ||
| Muscle spasms | 62/1487 (4.2%) | 20/742 (2.7%) | ||
| Osteoarthritis | 30/1487 (2%) | 23/742 (3.1%) | ||
| Myalgia | 89/1487 (6%) | 45/742 (6.1%) | ||
| Musculoskeletal pain | 40/1487 (2.7%) | 19/742 (2.6%) | ||
| Pain in extremity | 50/1487 (3.4%) | 16/742 (2.2%) | ||
| Nervous system disorders | ||||
| Dizziness | 65/1487 (4.4%) | 31/742 (4.2%) | ||
| Headache | 45/1487 (3%) | 24/742 (3.2%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 47/1487 (3.2%) | 23/742 (3.1%) | ||
| Dyspnoea | 19/1487 (1.3%) | 16/742 (2.2%) | ||
| Vascular disorders | ||||
| Hypertension | 42/1487 (2.8%) | 26/742 (3.5%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
If the Principal Investigator plans to publish information from the study, a copy of the manuscript should be provided to the Sponsor for review before submission for publication or presentation. The Sponsor may request that that publication be withheld.
Results Point of Contact
| Name/Title | Medical Director |
|---|---|
| Organization | Esperion Therapeutics, Inc. |
| Phone | 1-833-377-7633 |
| medinfo@esperion.com |
Responsible Party:
Esperion Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT02666664
Other Study ID Numbers:
- 1002-040
- 2015-004136-36
First Posted:
Jan 28, 2016
Last Update Posted:
May 11, 2020
Last Verified:
Apr 1, 2020